The proteases are a very broad group of enzymes which carry out an enzymatic function of hydrolyzing a peptide bond. See, e.g., Beynon (ed. 1989) Proteolytic Enzymes: A Practical Approach IRL Press, Oxford; Methods in Enzymology vols. 244 and 248. Within the group, there is a wide range of substrate specificities for the amino acids adjacent the cleavage sites. Proteases are typically categorized on the basis of their catalytic mechanisms, e.g., based upon studies of their active sites, or by the effects of pH. Four main categories of proteases are serine proteinases, sulfhydryl proteases, acid proteases, and metalloproteases. They may also be classified according to their sites of substrate cleavage, e.g., endoproteases, amino peptidases, or carboxy peptidases.
Proteases have traditionally held a large share of the industrial enzyme market. Proteases are used in many industrial processes, including in detergents and cleaning products, e.g., to degrade protein materials such as blood and stains, in leather production, e.g., to remove hair, in baking, e.g., to break down glutens, in flavorings, e.g., soy sauce, in meat tenderizing, e.g., to break down collagen, in gelatin or food supplement production, in the textile industry, in waste treatment, and in the photographic industry. See, e.g., Gusek (1991) Inform 1:14-18; Zamost, et al. (1996) J. Industrial Microbiol. 8:71-82; James and Simpson (1996) CRC Critical Reviews in Food Science and Nutrition 36:437-463; Teichgraeber, et al. (1993) Trends in Food Science and Technology 4:145-149; Tjwan, et al. (1993) J. Dairy Research 60:269-286; Haard (1992) J. Aquatic Food Product Technology 1:17-35; van Dijk (1995) Laundry and Cleaning News 21:32-33; Nolte, et al. (1996) J. Textile Institute 87:212-226; Chikkodi, et al. (1995) Textile Res. J. 65:564-569; and Shih (1993) Poultry Science 72:1617-1620.
Matrix metalloproteinases (MMPs) are a family of enzymes whose main physiological function is degradation of the extracellular matrix. See, e.g., Parsons, et al. (1997) Br. J. Surgery 84:160-166. These enzymes are present in normal healthy individuals and have been shown to have an important role in processes such as wound healing (see Wolf, et al. (1992) J. Invest. Dermatol. 99:870-872; and Wysocki, et al. (1993) J. Invest. Dermatol. 101:64-68), pregnancy and parturition (see Jeffrey (1991) Seminars Perinatol. 15:118-126), bone resorption (see Delaisse and Vaes, pp. 290-314 in Rifkin and Gay (eds. 1992) Biology and Physiology of the Osteoclast CRC Press, Ratan, Fla.), and mammary involution (Talhouk, et al. (1992) J. Cell Biol. 118:1271-1282). See also Nagase (1996) in Hooper (ed.) Zinc Metalloproteinases in Health and Disease Taylor and Francis, London. A recent focus on the MMPs is on their role in certain disease states in which breakdown of the extracellular matrix is a key feature, e.g., in rheumatoid arthritis (see Harris (1990) NEJ Med. 322:1277-1289), periodontal disease (see Page (1991) J. Periodont. Res. 26:230-242), and cancer (see Brown (1997) Medical Oncology 14:1-10; Chambers and Matisian (1997) J. NCI 89:1260-1270; Yu, et al. (1997) Drugs and Aging 11:229-244; Yu, et al. (1997) Clinical Pharmacology 11:229-244; Wojtowicz-Praga, et al. (1997) Invest. New Drugs 15:61-75; Coussens and Werb (1996) Chem. Biol. 3:895-904; and Talbot and Brown (1996) Eur. J. Cancer 32A:2528-2533).
While there are many uses for proteases, there is always the need for a more active or specific protease under various specific conditions. Alternatively, the distribution of these gene products may be useful as markers for specific cell or tissue types. There is a need for new proteinases of differing properties, specificities, and activities.